Arsenical compound.



II'ELLEB. msn'ro'm non mmmcu.

TION OI NEW YORK;

Specification o! lie'ttel 's Potent.

4mm; 11 mm moaned-nematn new! 311,: m 15., exogenous, mo mm 0 Mw mm- 1w. (WA convent m m-epueeono. i v

Patented Sept. 24,1915;

Ill'o nmwin Original lpplloation filed 0mm a, memo No. 104,400. Divided and um aii nmitn nled Ianuuy 18, 1918'. .Berislflo. 212,117.

To all whom it may concern: Be it known that we, Wnrgrnn A. Jnoona, .Ph D., iresidin at Mount Vernon Westchester county,

" I5 M. D., residing at Flushing; 1n the city 0 T9 I .ork, and LoUIsE PEARCE, .M.

lien York, bonou h of Queens, Queena county, NeweYork IGHAEL Hnmnnnnnonn,

1),, .resiflingin the city" boron in of. Manhattan, county and, State of D., residof New York, bo 'ou h' of and suite of',New ork,

nited States, have jointly z n' the city Menhnttamoount all citizens of the invented!: new and Improved Arsemcni 1 1:15 Compound, of'whichthefollowingis a speciiil on the new fioetiongxthis being a division-of our'epplioetifivmfierinl No. 194,460, fileddOotober 3, 191 i In th e course of onr researohe's and tests type of arsenieal compoundsof use-in the treatment of trype-nosornalor spii'ooheofnl infections; which we, describe in our co-pending applications, Serial Nos. 194,459 and 19% ,461, and whichrere composed of 2am nitqmatio ersonio acid possessing an au-nino uc lum'in side chainhaiing the em, oral forniu a NH.CI'IR.C( )NR'-R", in w ich It may be nlkyl or arlyt'l or=hyditogen, and R 'eml R'". maybe all I yin or hydrogen, the

"W" dramatic nucleus being joined to thee-ammo provoment,

side chain, we have found thnt in ceirtein instnnees, particularly in the treatment of -,spi 'oohpetal infections, H im-V in therapeutic group in said changed to the nreid oi- ,2 group orsubstituted ureid CONHGONHB gpioup',

whioh nuy curry an uttn'ched substituont.

, 'lhe substances were,

plivnyi, substituted phi-nyL'; in-nzyi or subew York, Ween H. newly acid with the of New York,

, o'wen-wes ob: tninoiiwhen tho mnid or CO B55201: wag

CO I O NH in which B may been alkyl or aryl Q 01" itswjtli whnlogenacyi strated the value of the two substanoesgdesignated as -N?)henylglycin-ureid-p-ersonic 5 ollowing 'formulag ecid with the following formula:

0 l Alf-on Thesesubstanoesand the others tobed-f scribed below represent in. new type 'of-iirsenical compounds.- The method of preperii tionis described as follows:

niinoph'enylureonic ioid dissolved in one lit 1" of normal" sodiui n" hygl 'oxid solntio'n'qo in. a'n,equeo\i""so1*n5 tion oreusponsion of any othei snitnbio besioi substance, are mixed with '135-*ohlo'ro'- aoetylnrea and the mixture-boiled-ioi 'on quarter o-fnn'hour, after which e heavy @60 of the erystalline prmluctsepai'a bexfi The? mixture is then heated for three-qnaftern-pf? an hour-on the water bath. Mwmmnng, the mixture is treated with-h dmeli-lom acid until theroactionis di's'tirictlyfaid w, Kongo red; The mixtureis then filteiedofl and; the residue washed well with ,Wa'ter tg For purification the'fl'pi'oduptlilnue nded in onv-hu'if a life! of water and um by droxid; :auldod until" Solution is oonipiete, The mm-tion of'thesolntion should'be-nem- 1 i345 trnl to-rlihnusx 'Ilh'e-mlution is thfinfilte and tlealzml,with. an exeess of-noeti o 217' grams of pa ti'ons being stable."

in I v 1s filtered, washed and dried. V

TlllS arsonlc acid is almost insoluble in water but is'readil'ly soluble in alkali and El kali carbonates. 8 solutions give u precipitate with the heavy metal salts. lioilin'gfl acids and alkalis hydrolyze it to phenyl I aim arsenic acid. It darkens above 230 but does not melt Below 280 C. It forms stable salts. The soluble metallic salts end particularly the sodium salt are most convenient for use.

The sodium salt is ing manner The acid is suspended in a smallvolume of warm water and carefully treated with 25 per cent: sodium hydroxid solution until solution is justcomplete. It is advisable to make the solution neutral to litmus. An equal volume of saturated aqeous sodium acetate is then added, causing the separation of the crystalline sodium salt. This is filpreparedin the follow- -tered off and purified by recrystallization,

from a small volume of hot water. The salt thus obtained ;,contains 2 molecules of water of crystallizzftion and dissolves readily in water.

Example I! ul-p-amonic (10M.

217 grams p -aminophenylarsonic acid are dissolved in one liter of normal sodium-hydroxid solutioh. 155 gm. a-chloroacctyl-f; methylurea are added and the mixture boiled for one hour. The chloro compound the reaction out.

After cooling, the mixture is treated with an excess of concentrated hydrochloric acid and filtered. The product, after washing. is purified as in Example I. 1

The sonic acid-is a color ess'crystallinc substance, practicallyinsoluble in cold water, some what soluble on boiling, casily soluble in alkali or alkali corhonatc, the neutral sol-u- 7 It is precipitated by acidsfrom its solutions and by heavy metal seltsjas insoluble salts. It decomposes at product suddenly crystal] i'zcs The sodium salt can be obtained, as in Example I. It is a stable,co'lorlcss crystaliss .droicid solution and treated with 50 line substance which dissolves readily in water and is recommended for use.

r 1 I a-yilwnylglycinureirllp I 43.4 grams p-aminophenylarsonie icid 'are dissolved in 200 cc. of normal-sodium hy phcnyl;chloracety'l urca'. (l l-l llllCllfl NHCONIL) 40 gm. sodium iodid, and 200.

cc. alcohol. The niixture'is boi ed under a re pure form as microscopic needles. This llmrfor several hours. talline reaction lowing formula ()n cooling the crysproduct; possessing the fol- 'is obtained. This is purified by redissolvnucleus being joined to theemmino group in said .side chain. gradually dissolves and during the reaction,

2. As a newfproduct; a soluble ,sa'lt'of an aromaticursonic acid having in "its inolecule an maminoar'ylumaside chain ln 'v'iug the general. formula- -N'll.(llIRKZONHUONR'II,

in which R is an-alkyl or a'iyl onhydiogcn and R. is :ilkyl, aryl or hydrogen, the aromatic nuclcus being joined 'to'the emunino groi'ip in said-side chain; V

3. As a new product, a soluble salt of an aromatic ursonicncidhaving in "its moleculc an a-aiuinoacylrn-ca side chain having the ,general formula ,Nll()ll'(.()Nll(IONIlR,

in'which R ishydrogen or alkyl or aryl.

-4. As a new prmluct, a solubl'salt of an Nsphenylglycin-{Z-uicthyl ureidii'rsonie acid. o. .a. new prmluct; a soluble salt of a id. r I I y r 6 .As ir newproduct, the 'sodium salt of an aromatic iii-sonic acid having in its molecule an a-aminoacylurea side chain; them-o.-

nmtienucleus being oined to the a-an iino group in saidside (ahaini As a new product. the sodium salt, of an aromatic arsonie acidlmving in its uiolecu c un ai-aminoiuzylurcu sidc'chu'iii having the general l'oriuula ----;\'ll.(ll ll.(()NllCU NR'II, inwhich It is an alkyl or aryl or hydro'gcn and R is alkyl, aryl or hydrogen,

i N phenylglycin metlhyli'n'cid pr ursonic the aromatic nucleus being joined to the a-amino group in said side chain.

8. As a new product, the sodium salt of an aronmtic arsenic acid having in its mg1e- 5 cule an cz-aminoncylm ea gide chain having the general formula -NHCHCONHGO NHR, in which R is hydrogen 01' alkyl or avryl. r

9. As a new product, the sodium salt of an f1N phenylglycin fi-methylm'eid masonic 10 M1 10. As a new product, thgmodiumn salt of N -1flmuylglycin -Q-1nethQ lureidp masonic acid.

WALTER A. JAUOBS, PH. 1). WADE ll. BROWN, M. 1). MICHAEL IlEIDELBERGER, PH. 1). LOUISE PEARCE, M. l). 

